GOLPH3 predicts survival of colorectal cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.
GOLPH3 predicts survival of colorectal cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.
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GOLPH3 可以预测接受基于 5-氟尿嘧啶的辅助化疗的结直肠癌患者的生存率。
DOI：
10.1186/1479-5876-12-15
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发表时间：
2014-01-21
影响因子：
7.4
通讯作者：
Su X
中科院分区：
文献类型：
--
作者：
Wang Z;Jiang B;Chen L;Di J;Cui M;Liu M;Ma Y;Yang H;Xing J;Zhang C;Yao Z;Zhang N;Dong B;Ji J;Su X
高尔基体磷蛋白3(GOLPH3)是一种与多种实体肿瘤的发生发展密切相关的癌基因，其过度表达与多种肿瘤的临床预后不良有关。然而，GOLPH3的表达与接受以5-氟尿嘧啶(5-FU)为基础的辅助化疗的结直肠癌(CRC)患者预后的关系尚不清楚。采用定量逆转录聚合酶链式反应(QRT-PCR)和免疫组织化学方法检测术后接受5-FU辅助化疗的结直肠癌组织中GOLPH3的表达。分析GOLPH3与临床病理特征及预后的关系。检测GOLPH3对结肠癌细胞株5-FU敏感性的影响。GOLPH3在结直肠癌组织中的表达高于配对的癌旁组织。Kaplan-Meier生存曲线显示，在接受以5-FU为基础的辅助化疗的患者中，GOLPH3的高表达与延长的无瘤生存期(DFS，P = 0.002)和总生存期(OS，P = 0.011)显著相关。多因素分析显示，GOLPH3表达是影响以5-FU为基础化疗方案的结直肠癌患者DFS的独立预后因素(HR，0.468；95%CI，0.222~0.987；P = 0.046)。在体外，过表达GOLPH3促进了5-FU的化疗敏感性，而siRNA介导的GOLPH3基因敲除降低了结直肠癌细胞对5-FU诱导的凋亡的敏感性。我们的结果表明，GOLPH3与结直肠癌术后5-FU为主的辅助化疗患者的预后有关，并可作为预测5-FU化疗敏感性的潜在指标。
Golgi phosphoprotein 3 (GOLPH3) has been validated as a potent oncogene involved in the progression of many types of solid tumors, and its overexpression is associated with poor clinical outcome in many cancers. However, it is still unknown the association of GOLPH3 expression with the prognosis of colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy. The expression of GOLPH3 was determined by qRT-PCR and immunohistochemistry in colorectal tissues from CRC patients treated with 5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5-FU sensitivity were examined in CRC cell lines. GOLPH3 expression was elevated in CRC tissues compared with matched adjacent noncancerous tissues. Kaplan-Meier survival curves indicated that high GOLPH3 expression was significantly associated with prolonged disease-free survival (DFS, P = 0.002) and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was an independent prognostic factor for DFS in CRC patients treated with 5-FU-based chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA-mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced apoptosis. Our results suggest that GOLPH3 is associated with prognosis in CRC patients treated with postoperative 5-FU-based adjuvant chemotherapy, and may serve as a potential indicator to predict 5-FU chemosensitivity.
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